"In a normal individual, light touch or small temperature changes are innocuous events," he explained. "But with neural injury there is a condition called allodynia in which the person experiences excruciating pain from such normally non-painful stimuli."
Dr. Loomis thinks that a major site for this dysfunction lies in the spinal cord. "There are neurons within the spinal cord that normally modulate the sensory information that arrives there. We have evidence that changes within the spinal cord that occur after injury of a peripheral nerve are responsible for this allodynia."
Dr. Loomis' project is designed to examine the hypothesis that the allodynia results from damage to, or loss of, glycine interneurons in the spinal cord. "They normally modulate the response of sensory neurons to light tactile stimuli or modest temperature changes. If they are damaged or become dysfunctional these stimuli can trigger a response in the brain which appears to be pain -- it's a misinterpretation of the information that's arriving in the spinal cord."
To study this phenomenon, Dr. Loomis has developed an experimental animal model in which the glycine neurons are pharmacologically blocked with intrathecal strychnine, thus reproducing many of the features of neural injury pain. "We don't have to injure the animal in order to produce this model -- that overcomes some of the ethical issues that are always associated with animal experiments of chronic pain and nerve injury."
Two years ago Dr. Loomis, with Dr. Detlef Bieger, received a $25,000 Dr. Albert R. Cox Research Grant Award to develop the animal model on which this current MRC-funded research is based. "What we want to do now is validate that model," said Dr. Loomis. "We'll do that by making an injury in the spinal cord to see if the glycine neurons are really damaged and if there is pain from the injury -- we want to see if the spinal pharmacology of that injury model is comparable to our strychnine model. If it is, that means we can use the strychnine model for further studies of the spinal pharmacology of allodynia and for testing putative anti-allodynic drugs."
Dr. Loomis emphasizes that this project is basic research designed to expand understanding of abnormal pain states and the changes in sensory processing that underlie allodynia. But he also feels that it may eventually lead to clinical outcomes. "If we knew which particular types of neurons were being damaged as a result of nerve injury we could target ways of trying to preserve those neurons after injury."